Expression of non-classical HLA-E molecules by immune cells in B-cell derived blood cancers

Pashkina E.A., Denisova V.V., Skachkov I.P., Boeva O.S., Kozlov V.A.

Federal State Budgetary Scientific Institution "Research Institute of Fundamental and Clinical Immunology", Novosibirsk, Russia

In addition to the classical molecules of the major histocompatibility complex (MHC) class I, HLA-A, HLA-B and HLA-C, which are extremely polymorphic, there are also non-classical molecules with an extremely limited number of allelic variants. Non-classical molecules include HLA-E, which is represented by only two allelic variants. This molecule, like classical MHC molecules, plays a significant role in the immune response due to its participation in the presentation of peptides during immunological surveillance. HLA-E is capable of presenting peptides from classical MHC class I molecules, “presenting” them to NK cells, and also performing a number of other functions when interacting with immunocompetent cells. Depending on various factors, HLA-E can inhibit or activate immunocompetent cells. This molecule is expressed by mononuclear leukocytes, namely T and B lymphocytes, monocytes and macrophages, as well as tumor cells. Currently, HLA-E is known to contribute to a number of oncological diseases, including leukemia and lymphoma, so the aim of this study was to evaluate HLA-E expression by immune cells of patients with various hemoblastoses. Our data indicate that statistically significant changes in HLA-E expression on immunocompetent cells are observed during the development of B-cell leukemia, multiple myeloma (MM) and mantle cell lymphoma (MCL). The proportion of T lymphocytes carrying HLA-E on their surface was approximately 2.5 times higher in patients with MM and MCL compared to healthy individuals from the control group. At the same time, among monocytes in MM, an increase in the proportion of cells expressing HLA-E was observed, whereas in MCL this indicator decreased. Our results indicate a potential role of HLA-E expression on healthy immune cells in the formation of the tumor microenvironment and maintaining immunosuppression against tumor cells in such forms of hemoblastoses as MM and MCL.